The objective of this project is the study of basic biophysical processes which affect the electrical activity of the heart, and determine its reflection in epicardial and body surface potentials. This will be achieved through the use of theoretical (computer) model simulations. Specific aims are: (1) The reconstruction of epicardial potentials from body surface potential distributions. This will permit a non-invasive, detailed examination of regional electrical events within the heart (site of origin of arrhythmias, location and size of ischemic and infarcted regions, nature of conduction abnormalities. This procedure will provide non- invasively, diagnostic information regarding electrical disturbances of the heart. It could, in many cases, replace invasive epicardial mapping during surgery for the purpose of localization of abnormal myocardial regions prior to surgical ablation. In addition, it will constitute a useful tool for non- invasive, experimental studies in the intact animal of normal and abnormal cardiac electrical activity and of changes in its pattern due to various interventions (drugs, neural stimulation, etc.) (2) Studies of propagation of electrical excitation in cardiac muscle using 1- and 2-dimensional models of the tissue. Our preliminary results demonstrate the importance of the tissue structure in determining the nature of propagation and in creating conditions that lead to arrhythmogenesis (slow conduction, unidirectional block, changes in action potential duration). Studies of reentry and its underlying mechanism will continue in a ring-shaped model. Properties of normal and abnormal propagation will be studied in a 2-dimensional model based on realistic anatomy (realistic cell size, an intercalated disc model connecting adjacent cells, different distribution of cell connections transverse and longitudinal to the fiber axis). In particular, anisotropy and structural effects due to changes in the degree of cell-to-cell coupling (such as occur in ischemia and infarction) will be simulated, and their importance in creating reentry will be evaluated. (3) The generation of activation isochrones and the computation of epicardial and body-surface potential distributions in a whole-heart/torso model which contains a representation of the specialized conduction system and of fiber orientation. Simulations will be performed for the normal heart and for various abnormalities. The results will help relate surface and epicardial potentials to underlying electrical events in the heart.